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一个精细平衡的秩序-混乱平衡,雕塑了抗生素绑定蛋白质的折叠结合景观

Lawanya Natarajan¹, Maria Laura De Sciscio², Alessandro Nicola Nardi²

¹Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, India.

Proceedings of the National Academy of Sciences of the United States of America

|May 6, 2024

概括

TipAS是一种抗生素结合蛋白质,存在于多个状态,部分折叠的形式使抗生素封存成为可能. 这种分子灵活性对于MerR家族蛋白质赋予抗生素耐药性至关重要.

科学领域:

生物化学生物化学
分子生物学分子生物学
结构生物学结构生物学

背景情况:

TipA是来自*Streptomyces lividans*的MerR家族转录因子,通过隔离类抗生素来赋予抗生素耐药性.
蒂帕斯 (TipAS) 是TipA的一种异型,它包含一个部分无序的N-终端子域,该子域在抗生素结合时折叠,这表明它在乱交结合和功能中的作用.
了解TipAS的分子异质性对于阐明抗生素隔离机制至关重要.

研究的目的:

研究TipAS蛋白质的分子异质性和结构动态.
阐明TipAS对抗生素结合和封存的机制.
确定MerR家族抗生素隔离蛋白中部分障碍的功能和进化意义.

主要方法:

均衡和时间解决的实验.
统计建模. 统计建模.
分子模拟. 分子模拟.

主要成果:

原生TipAS组合存在于约束无能和约束有能力的子状态之间的预平衡中.
具有部分结构化的N端的结合能力状态,随着温度的增加而失去结构,并表现出缓慢的形状交换.
抗生素的结合,比如对列的结合,通过混合诱导适合/符合性选择机制发生,稳定结合竞争的基质.
这些整体特征被保存在来自人类病原菌的ortologs中.

结论:

提帕斯原生组合中的部分内在障碍对于其抗生素隔离功能至关重要.
提帕斯的动态构造格局使其与多种抗生素的相互作用更加容易.
保存的组合特征突出了MerR家族抗生素耐药性蛋白中部分障碍的功能重要性.

关键词:

结合抗生素的抗生素结合这是一种混乱的混乱,一种混乱的混乱.动力学动力学动力学折叠功能功能热力学热力学热力学

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